Methods for treating, maintaining, or improving fur or hair pigmentation of domestic carnivores using a composition comprising free tyrosine

ABSTRACT

The present invention relates to a food composition for domestic carnivores which makes it possible to prevent or correct pigmentation abnormalities and/or to improve the quality of the fur of the said domestic carnivores, characterized in that it contains a source of free tyrosine representing at least 5% of the total tyrosine supplied. The invention also relates to a method for preventing or correcting pigmentation abnormalities of the fur of domestic carnivores that uses said food composition.

This application is a continuation of U.S. application Ser. No.09/703,522, filed Nov. 1, 2000, now U.S. Pat. No. 6,641,835, whichclaims the priority of French Application No. FR 9913657, filed Nov. 2,1999, which applications are incorporated herein by reference in theirentirety.

The present invention relates to a food composition for domesticcarnivores which makes it possible to prevent or correct pigmentationabnormalities and/or to improve the quality of the fur of the saiddomestic carnivores, characterized in that it contains a source of freetyrosine representing at least 5% of the total tyrosine supplied. Theinvention also relates to a veterinary composition containing tyrosine,as well as the use of free tyrosine for the preparation of a food and/orveterinary composition intended for preventing pigmentationabnormalities and/or for improving the quality of the fur in a domesticcarnivore.

Despite a rich and nutritionally well-balanced diet, in particular asregards the supply of proteins and amino acids, many breeders or ownersof domestic carnivores, particularly dogs and cats, complain ofabnormalities in the pigmentation of their animals.

These “discolorations” cause them substantial financial losses,particularly during competitions, the animals displaying theseabnormalities being systematically downgraded or even eliminated by“judges” who know the “standards” of each breed of animal well.

Domestic carnivores designate dogs and cats, but also other animalspecies, and particularly animals having a coat, mink, fox, sable andthe like.

These poor pigmentations may occur in the skin, the mucous membranes,the eyes, and more frequently in the hair.

The normal colour of these organs is the visual result of the depositsof several sorts of pigments:

-   -   nonmelanic pigments: blood pigments (oxyhaemoglobin, reduced        hemoglobin, haemosiderin), carotene and its derivatives;    -   melanic pigments or melanins (eumelanins, phaeomelanins,        trichochromes) (E. Guaguère et al., Le Point Vétérinaire, 1985,        vol. 17, No. 93, 549-557).

Among these pigments, it is mainly the eumelanins which give the blackcolour or the dark shade of the pigmentation of the organs.

It is known that the melanins are synthesized by organelles calledmelanosomes of the specialized cells called melanocytes, from tyrosine,a “semi-essential” aromatic amino acid supplied by the dietary proteins.An amino acid is said to be “essential” when it is necessarily suppliedby a source which is external to the animal, because the latter itselfdoes not know how to produce it. Thus, tyrosine is “semi-essential”because the animal can synthesize it from another “essential” aromaticamino acid, phenylalanine. Consequently, for example, the NationalResearch Council (N.R.C.) of the United States of America, which is theworld authority on animal nutrition, recommends the followingnutritional standards for cats and dogs, based on the dry matter contentof the foods, and of which only phenylalanine is considered as beingessential (Nutrient Requirements of Cats, 1986; Nutrient Requirements ofDogs, 1985):

Cats Dogs Proteins  240 g/kg (that is 24%) Not indicated Phenylalanine +tyrosine  8.5 g/kg (that is 0.85%) 0.72% Of which phenylalanine   4 g/kg(that is 0.4%) ≧50% of Phe + Tyr

These standards have nevertheless currently been widely overtaken bybalanced industrial foods which are considerably richer in proteins andin amino acids, and have consequently already a high content oftyrosine.

Yet, in spite of the richness of the current foods supplied by all themajor international brands, breeders frequently complain of thepigmentation abnormalities in their animals, and particularly in theirfur. Breeders and vets speak in this case of “decolorization”, of“discoloration”, of “depigmentation”, of “dispigmentation”, of “redhair”, of “yellow hair”, of “faded hair”, and the like, to designatethis syndrome.

The nutritional etiology of this syndrome is commonly excluded by vetsand nutritionists (L. Case et al., Canine and Feline Nutrition, 1995,Mosby Ed., Saint Louis, USA, p 316-319). Particularly, Paragon andGranjean (Rec. Vét. Méd., 1992168(10), 769-77) have excluded a possibledeficiency of tyrosine in dogs and cats normally fed in practicalconditions.

Only one team in the Ecole Nationale Vétérinaire de Toulouse hasdescribed in dogs a “rubra-pilaris syndrome” or red hair disease whichcan have a nutritional cause (P. Dorchies et al., Revue de MédecineVétérinaire, 1979, 130 (10), 13711382). Indeed, the syndrome isaccompanied by an increase in the level of blood and urinary indican.This high presence of indican in the blood and the urine is a sign of apoor digestive use of an essential amino acid, tryptophan, becauseindican or potassium indoxylsulphate is a metabolite which issynthesized by the bacteria in the large intestine from dietarytryptophan.

The applicant has discovered that this phenomenon of pigmentationabnormality is due to a deficiency in free tyrosine in the diet.

The applicant has indeed discovered that in order to preventpigmentation abnormalities and/or correct them when they exist indomestic carnivores fed with current balanced foods which have aromaticamino acids, in particular tyrosine, supplied well above the knownrecommended standards (such as those of N.R.C., for example), it isessential that part of the tyrosine is supplied to the animal in freeform and that the tyrosine supply does not exist solely and completelyin bound tyrosine form. This discovery is valid regardless of the levelof aromatic amino acid contents in the foods, provided that they areequal to or above the recommended nutritional standards.

Conventionally, an amino acid is said to be “bound” when it is embeddedin the structure of a protein. To be able to assay a bound amino acid,the protein should be previously and completely hydrolyzed, most oftenwith a protease or a strong acid or a strong base. This is the case forthe amino acids supplied by the proteins in the dietary raw materialscommonly used, whether they are of animal or plant or microbial orfungal origin.

An amino acid is said to be “free” when its assay does not require priorhydrolysis with a protease or a strong acid or a strong base. To assay afree amino acid in a food, it must simply be separated from thestructured proteins by precipitating them, with a protein coagulant suchas trichloroacetic acid or sulphosalicylic acid for example. Afterseparating the structured proteins, the free amino acid can then beassayed by any known means, such as liquid chromatography for example.

The applicant has discovered, surprisingly, that when at least 5% of thetotal supplied tyrosine, and still more preferably at least 10%, 15%,20%, 25% or 30% is supplied to the animal in free form, it is possibleto prevent the pigmentation abnormalities in domestic carnivores and/orto treat them when they exist. It is necessary for the free tyrosine tobe supplied to the animal, regardless of the quantity of bound tyrosinesupplied.

Thus, the invention relates to a domestic carnivore food composition forpreventing pigmentation abnormalities and/or improving the quality ofthe fur, characterized in that it contains:

-   -   at least one source of proteins of animal or plant origin,        and/or    -   at least one source of fatty substances of animal or plant        origin, and/or    -   at least one source of rapid or slow carbohydrates, in        particular cereals, and    -   one source of free tyrosine representing at least 5% of the        total tyrosine supplied.

In another embodiment of the invention, the free tyrosine level in thefood composition will be greater than 10% of the total tyrosinesupplied.

In another embodiment, the food composition already contains a level oftyrosine that is well above the nutritional standards as mentionedabove.

The invention also relates to a domestic carnivore veterinarycomposition for preventing pigmentation abnormalities and/or improvingthe quality of the fur, characterized in that it contains a source offree tyrosine representing at least 5%, and preferably at least 10%,15%, 20%, 25% or 30% of the total tyrosine supplied in the diet.

The applicant has therefore developed a method for preventingpigmentation abnormalities and/or improving the quality of the fur indomestic carnivore, characterized in that a quantity of free tyrosinegreater than 5%, or preferably 10%, 15%, 20%, 25% or 30% of the quantityof total tyrosine supplied in the diet of the said carnivore isadministered to the said carnivore. This process, notably for itsesthetic result, is also one of the subjects of the present invention.

The food compositions according to the invention may be dry foods suchas biscuits for example, semi-moist foods, for example pates and thelike, or moist foods. These foods also comprise snacks, treats orextruded foods, as well as nutritional supplements.

The veterinary compositions according to the invention includecompositions which can be administered by the oral, parenteral or dermalroute. Preferably, the veterinary composition will be administered bythe oral or parenteral route or by the gastrodigestive system. Thus, theveterinary composition according to the invention may be in particular,without this list being limiting, an intragastric, intraintestinal,intramuscular, subcutaneous or intravenous infusion, a hard gelatincapsule, a pill, a soft gelatin capsule, a bolus, a suppository or anyother presentation which can be administered by the digestive route.

Conventional excipients may be added to this veterinary composition,such as gelatin, starch, lactose, magnesium stearate, talc, gum arabicand the like.

The free tyrosine supply may consist of L-tyrosine and/or its salts.Commercially available L-tyrosine may be obtained by extraction afterenzymatic or chemical hydrolysis of various animal, plant, microbial orfungal proteins or by any other process known to amino acid producers.It is also possible to use as free tyrosine source a protein which iscompletely or partially hydrolyzed (with a protease, an acid or a base),whether the original protein is of animal, plant, microbial or fungalorigin, without the free tyrosine being separated from the rest of theamino acids.

The applicant has also discovered that, particularly in the fur ofanimals, the supply of free tyrosine improves not only the pigmentationbut also the quality of the fur, mainly the density and the length ofthe hair.

The examples which follow are intended to illustrate some aspects of theinvention without, however, being limiting.

EXAMPLES Example 1

The protein, free tyrosine and bound tyrosine levels of dog and catfoods representative of the well known brands on the world market areassayed. The assays were performed according to the standard methods ofthe Laréal laboratory, 56250 Saint Nolff, France which is accredited bythe French Committee on Accreditation more generally known under thename COFRAC (Accreditation Number: 1 285). Particularly, the boundtyrosine and the free tyrosine were assayed according to the AFNOR(Association Française de Normalisation) standard method XP V 18-113(January 1988).

The assays showed that no free tyrosine is present in the commerciallyavailable foods. Only bound tyrosine could be assayed.

The results obtained on the crude foods are the following:

Proteins (%) Bound tyrosine (%) Dog foods: Eukanuba Puppy 31.1 1.04Eukanuba Junior 26.1 0.85 Eukanuba Premium 30.3 1.02 Eukanuba Regular27.6 0.82 Hill's Growth 25.6 0.95 Hill's Maintenance 22.8 0.87 Hill's M.Light 16.1 0.57 Hill's Senior 16.2 0.56 Proplan Puppy 29.3 1.25 ProplanAdult 26.5 1.05 Proplan Light 26.9 1.02 Proplan Senior 25.6 0.93 RoyalCanin Mini Junior 32.8 0.92 Royal Canin Adult 1 27.5 0.83 Royal CaninAdult 2 27.4 0.80 Royal Canin Medium Junior 25.7 0.79 Royal Canin MediumAdult 1 25.7 0.81 Royal Canin Medium Adult 2 25.6 0.81 Royal Canin MaxiJunior 35.7 0.98 Royal Canin Maxi Adult 1 25.5 0.75 Royal Canin MaxiAdult 2 26.2 0.78 Cat foods: Iams Chicken 32.6 1.11 Iams Kitten 34.11.06 Hill's Growth 34.7 1.29 Hill's Maintenance 31.2 1.12 Hill's Senior29.9 1.23 Proplan Kitten 33.7 1.23 Proplan Adult 33.5 1.39 Proplan Light33.9 1.49 Royal Canin Kitten 34 33.1 1.04 Royal Canin Sensible 33 33.11.07 Royal Canin Senior 28 28.6 1.11

These results show that the commercially available dog and cat foods arevery rich and widely exceed the standards recommended by N.R.C., mainlyfor the tyrosine supplies. However, in all these foods, the tyrosineexists completely in the bound form.

Example 2

An experimental complete food for domestic carnivores, presented in theform of extruded foods, and in which the composition of the rawmaterials is the following (%), was manufactured:

Animal proteins 31 Rice 24 Maize 5 Vegetable by-products 13.6 Fats andoils 16.2 Flavourings 4 Fishmeal 2 Vitamin-mineral premixes 4Commercially available L-tyrosine 0.2 Total 100

The L-tyrosine provided by the company B.C.F., 56140 Pleucadeuc, France,has a free tyrosine titre of 97%, which means that 0.2% provides 0.19%of free tyrosine in the food.

The analytical characteristics of the food are the following:

Proteins   30% Fatty substances   22% Calcium 0.80% Phosphorus 0.75%Cellulose 4.50% Metabolizable energy 4340 kcal/kg Phenylalanine 1.30%Bound tyrosine 1.04% Free tyrosine 0.19% Total tyrosine (bound + free)1.23% (Free tyrosine/total tyrosine) × 100 15.4%

This experimental food was distributed to cats on two specialized farms.At the end of the trials which lasted for 6 months on the first farm and4 months on the second farm, the observations on the fur of the animals,made by specialist breeders and experienced technicians, are thefollowing, with respect to the desired standards for these animals:

Number Qualities Length Farm of cats Pigmentation of the fur of the hairM . . . 5 Very black, Dense Long without any discoloration C . . . 7Dark, intense, Dense, soft to Long without any the touch, easydiscoloration to disentangle

These results show that the experimental food, during many months oftrials, prevented any problem of discoloration which is often found onthis type of specialized farms from occurring. In the same manner, thequalities of the fur were judged to have improved compared with cats fedwith the previously used foods, which are commercially available foodscontaining no free tyrosine.

Example 3

A 7-year-old female cat of “Tricolour Persian” breed was fed withcommercially available foods containing no free tyrosine. This femalecat exhibited abnormalities in its fur compared with the standards forits breed: “faded” black hair and excess of “reddish yellow” hair.

The experimental food of Example 2, containing free tyrosine, was givento this female cat. After four and a half months of trial, the “fadedhair” become dark and the “reddish yellow” hair defect decreased.

This example shows that a food containing free tyrosine was able tocorrect the pigmentation abnormalities in a domestic carnivore.

Example 4

Four black-haired cats, were suffering of the “red hair syndrome”, whilebeing fed with the commercial diet S9 Felistar® (originating from RoyalCanin).

Analysis of this food composition shows that it is a balanced food veryrich in protein content and that the level of tyrosine is well above therecommended needs for cats:

Proteins   31% Tyrosine 1.10%

Further analysis of this food shows that the tyrosine is comingexclusively from the structured proteins of the raw materials. Thetyrosine present in this food is therefore completely “bound”.

After a detailed veterinary examination, these cats received the samefood composition, enriched in free tyrosine. The levels of the differentforms of tyrosine in this composition are as follow:

Bound tyrosine 1.10% Free tyrosine 0.43% Total tyrosine 1.53%

The colors of the cats' coats were as described in the following table:

Color of the coat Age Day Day Day Day Day Day Cat Sex (Years) 0 28 59 98134 212 Charbon M 9 R R R B B B Jeep M 6 R B B B B B Iris F 7 R B N.A. BB N.A. Fida F 8 R B B B N.A. N.A. M = male, F = female, R = red, B =black, N.A. = non available

These results show that addition of free tyrosine in a commercial dietleads to an improvement in the color of the coat of cats suffering fromthe “red hair syndrome”.

1. A domestic carnivore food composition for treating or correctingpigmentation abnormalities and/or improving the quality of the fur,comprising: at least one source of protein of animal or plant origin,and/or at least one source of fatty substances of animal or plantorigin, and/or at least one source of carbohydrates, and one source offree tyrosine representing at least 5% by weight of the total tyrosinesupplied in the food composition.
 2. The food composition of claim 1,wherein the free tyrosine level is greater than 10% of the totaltyrosine supplied in the food composition.
 3. The food composition ofclaim 1, wherein the domestic carnivore is chosen from cats, dogs,minks, foxes or sables.
 4. The food composition of claim 1, wherein theamount of free tyrosine is at least 10%, 15%, 20%, 25%, or 30% by weightof the total amount of tyrosine in the food composition.
 5. The foodcomposition of claim 1, wherein the food composition is a cat foodcomposition.
 6. The food composition of claim 1, wherein the foodcomposition is a dog food composition.
 7. The food composition of claim1, wherein the food composition is a mink food composition, a fox foodcomposition, or a sable food composition.
 8. The food composition ofclaim 1, wherein the color of the hair or fur is black.
 9. The foodcomposition of claim 5, wherein the cat food composition meets thestandard of Nutrient Requirements of Cats as published by the NationalResearch Council of the United States of America.
 10. The foodcomposition of claim 6, wherein the dog food composition meets thestandard of Nutrient Requirements of Dogs as published by the NationalResearch Council of the United States of America.
 11. The foodcomposition of claim 1, wherein the food composition has a level ofamino acids equal to or above acceptable nutritional standards.
 12. Thefood composition of claim 1, wherein the food composition is anutritionally well-balanced food composition.
 13. The food compositionof claim 1, further comprising a source of bound tyrosine.
 14. The foodcomposition of claim 13 wherein the bound tyrosine is in the source ofprotein.
 15. A domestic carnivore food composition for treating orcorrecting pigmentation abnormalities and/or improving the quality ofthe fur, comprising: (a) a source of bound tyrosine; and (b) a source offree tyrosine, wherein the amount of free tyrosine is at least 5% byweight of the total amount of tyrosine in the food composition.
 16. Thefood composition of claim 15 wherein the amount of free tyrosine is atleast 10%, 15%, 20%, 25%, or 30% by weight of the total amount oftyrosine in the food composition.
 17. The food composition of claim 15wherein the food composition is a cat food composition.
 18. The foodcomposition of claim 15 wherein the food composition is a dog foodcomposition.
 19. The food composition of claim 15 wherein the foodcomposition is a mink food composition, a fox food composition, or asable food composition.
 20. The food composition of claim 15 wherein thecolor of the hair or fur is black.
 21. The food composition of claim 17wherein the cat food composition meets the standard of NutrientRequirements of Cats as published by the National Research Council ofthe United States of America.
 22. The food composition of claim 18wherein the dog food composition meets the standard of NutrientRequirements of Dogs as published by the National Research Council ofthe United States of America.
 23. The food composition of claim 15wherein the food composition has a level of amino acids equal to orabove acceptable nutritional standards.
 24. The food composition ofclaim 15 wherein the food composition is a nutritionally well-balancedfood composition.